皮肤鳞状细胞癌的外科治疗

目的 探讨皮肤鳞状细胞癌的外科治疗方法及效果。方法 收集1981年12月至2011年12月鳞状细胞癌105例,其中手术治疗101例。切除病灶后,根据创面不同部位、大小、深度,选择任意皮瓣、肌皮瓣或皮片修复创面;创面位于面部及关节部位采用分区植皮方法。结果病灶切除后,移植皮片48例,任意皮瓣或肌皮瓣修复53例;随诊6个月以上85例,随诊5年以上52例,16例发生局部复发或远处转移,其中8例死亡,其余患者术区外形良好,局部无复发。结论 皮肤鳞状细胞癌早期发现行完整手术切除仍然是最佳的治疗手段,对手术缺损可以采用整形美容方法修复,实现患者的生存时间和生活质量的提高。     

局部进展期食管鳞癌全新辅助治疗可行方案的探索

新辅助放化疗联合手术为局部进展期食管癌患者的标准治疗方案, 这一治疗方案已得到广泛应用, 其疗效也已得到临床医师的认可。然而, 即使是完成了新辅助放疗和随后的手术治疗, 仍有部分患者在短期内出现局部区域复发和/或远处转移, 其中远处转移成为新辅助放化疗后接受手术患者的主要失败模式, 这从另一方面说明该模式还有进一步改善的必要。借助于直肠癌患者从全新辅助治疗模式中获益的经验, 本文探讨了局部进展期食管癌患者进行全新辅助治疗的可能性及其实施方案。     

Drug therapy in advanced squamous cell carcinoma of the ORL region

This paper reviews the role of chemotherapy in advanced squamous cell carcinoma of the head and neck region (SSCHN). Two different areas of administration are discussed separately: (1) Palliative therapy in recurrent disease, and (2) chemotherapy as additional measure in first line treatment of advanced SSCHN aiming at an increase of the disease-free survival and the cure rate. Overall response rates of 80% and complete clinical remissions in about 40% of the cases can be achieved in locally untreated tumors. On the other hand, recurrent SSCHN respond not as well to chemotherapy; nevertheless, a good temporary palliative effect is reached in more than half of the patients. As example for the numerous combination programs studied in the last few years, we report some data of the two protocols evaluated at our clinic, cis-diamminedichloroplatinum/adriamycin and methotrexate/5-fluorouracil, respectively.     

Sentinel node biopsy for high-risk cutaneous squamous cell carcinoma

Aim

The use of sentinel node biopsy (SNB) has not been established for cutaneous squamous cell carcinoma (SCC), and its clinical significance has not been clarified. We investigated the usefulness of and indication criteria for SNB for cutaneous SCC.

Materials and methods

Twenty-six patients with high-risk cutaneous SCC that had undergone SNB were retrospectively reviewed. SNB was performed with either the dye method or a combined dye and radioisotope method.

Results

Of the 26 patients, recurrence or metastasis was observed in 5 cases (19.2%). Six cases (23.1%) were sentinel node (SN) metastasis-positive. All cases that were SN metastasis-negative survived, and 4 of 6 SN metastasis-positive (66.7%) cases died of the original disease. The 3-year survival rates of all cases, SN metastasis-negative cases, and SN metastasis-positive cases were 82.2%, 100%, and 20.8%, respectively. Tumour thickness was a significant risk factor for SN metastasis (p = 0.049). Recurrence occurred in 4 of 7 cases involving external genitalia, 3 of which died. The 3-year survival rates of external genitalia and nongenital cases were 47.6% and 94.1%, respectively (p = 0.016).

Conclusions

SNB aided the early discovery and treatment of latent lymph node metastasis and helped predict whether SN metastasis had occurred, and therefore helped predict patient prognosis. These results suggest that thickness of the primary lesion is an indication criterion for the use of SNB in cases of cutaneous SCC. SNB should be considered in cases where tumour thickness is ≥2 mm and actively performed in cases ≥5 mm.     

皮肤鳞状细胞癌研究进展

鳞状细胞癌在皮肤非黑色素细胞性恶性肿瘤中发病率居第二位,近年来发病率呈增高趋势。鳞状细胞癌病因复杂且临床表现无特异性,有时易导致误诊。虽然鳞状细胞癌通常生长较慢,但一些特殊类型可较早发生侵袭、转移。近年来,人们对鳞状细胞癌的认识逐渐深入,在其诊断、治疗、预防等方面研究成果显著。本文就鳞状细胞癌流行病学、病因、临床表现及病理、临床分期、治疗及预后等方面进行综述。     

皮肤鳞状细胞癌治疗靶点的研究进展

作为一种常见的非黑色素瘤皮肤癌,晚期皮肤鳞状细胞癌（cutaneous squamous cell carcinoma,cSCC）的治疗仍是急需 解决的临床难题。尽管cSCC并非靶向治疗研究的重点,但近年来随着靶向治疗在其他肿瘤的研究和应用的深入,cSCC的靶向 治疗也取得新的进展,特别是针对PD-1的免疫检查点疗法已经获准进入临床应用;针对另一些靶点如细胞表皮生长因子受体 （EGFR）、血管内皮生长因子受体（VEGFR）、胰岛素样生长因子受体（IGFR）以及肿瘤抗原MAGE-A3等的疗法也正在临床试用; TP53、CDKN2A和Notch等cSCC频繁突变的基因,以及RAS-RAF-MEK-ERK与PI3K-AKT-mTOR等通路相关信号分子和端粒酶 等也是具有研发潜力的cSCC治疗靶点,针对这些靶点开展深入研究有可能为cSCC的治疗找到新的途径。     

Combined-modality treatment for advanced oral tongue squamous cell carcinoma

PURPOSE: The aim of this study was to investigate prognostic factors in advanced-stage oral tongue cancer treated with postoperative adjuvant therapy and to identify indications for adjuvant concomitant chemoradiotherapy (CCRT). METHODS AND MATERIALS: We retrospectively reviewed the records of 201 patients with advanced squamous cell carcinoma of the oral tongue managed between January 1995 and November 2002. All had undergone wide excision and neck dissection plus adjuvant radiotherapy or CCRT. Based on postoperative staging, 123 (61.2%) patients had Stage IV and 78 (38.8%) had Stage III disease. All patients were followed for at least 18 months after completion of radiotherapy or until death. The median follow-up was 40.4 months for surviving patients. The median dose of radiotherapy was 64.8 Gy (range, 58.8-72.8 Gy). Cisplatin-based regimens were used for chemotherapy. RESULTS: The 3-year overall survival (OS) and recurrence-free survival (RFS) rates were 48% and 50.8%, respectively. Stage, multiple nodal metastases, differentiation, and extracapsular spread (ECS) significantly affected disease-specific survival on univariate analysis. On multivariate analysis, multiple nodal metastases, differentiation, ECS, and CCRT were independent prognostic factors. If ECS was present, only CCRT significantly improved survival (3-year RFS with ECS and with CCRT = 48.2% vs. without CCRT = 15%, p = 0.038). In the presence of other poor prognostic factors, results of the two treatment strategies did not significantly differ. CONCLUSIONS: Based on this study, ECS appears to be an absolute indication for adjuvant CCRT. CCRT can not be shown to be statistically better than radiotherapy alone in this retrospective series when ECS is not present.     

Treatment of unresectable and metastatic cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (SCC) is an already common disorder with a rapidly increasing incidence. Treatment of early disease depends primarily on surgery or destructive techniques. In contrast to the frequency of early SCC, unresectable or metastatic SCC is relatively rare, but potentially life-threatening without clearly proven treatment options. Few rigorous studies of the treatment of advanced SCC have been undertaken. In the past, various agents have been explored in a limited fashion, including chemotherapy (cisplatin, fluoropyrimidines, bleomycin, doxorubicin), 13-cis-retinoic acid, and interferon-α2a. Clinical activity has been suggested by these trials, but their small sizes, heterogeneous patient populations, and lack of randomization have hindered the use of their results in defining treatment paradigms. Only one rigorous randomized trial has focused on cutaneous SCC. Enrolling 66 patients, that trial randomized patients at high recurrence risk to either observation or postoperative interferon-α2a and 13-cis-retinoic acid. This treatment did not improve time to recurrence or prevent secondary cutaneous SCC from developing. Though not in the metastatic setting, this study casts doubt on the ability of this regimen to control metastatic disease. Recently, agents targeting the human epidermal growth factor receptor (erlotinib, gefitinib, cetuximab) have displayed preliminary evidence of activity in phase II clinical trials and case series reports. Expression of this receptor is frequent in cutaneous SCC and appears to be prognostically adverse. Only the conduct of rigorous trials, with well-defined endpoints, adequate patient numbers, and preferably randomization, can prove the clinical efficacy of this promising treatment approach and define better therapy for this vexing clinical problem.     

微小RNA在皮肤鳞状细胞癌中的研究进展

皮肤鳞状细胞癌(cSCC)是角质形成细胞来源的恶性肿瘤之一。转录组是特定条件下细胞内全部转录产物的总和,包括编码mRNA和非编码RNA。研究发现,与正常细胞相比,鳞癌细胞在基因转录水平和模式上存在很大差异,具有不同转录表达谱。微小RNA(miRNA)可通过抑制转录产物的翻译,从而调控靶基因的表达,影响cSCC细胞的增殖、分化和凋亡等病理过程。越来越多的研究表明,miRNAs作为cSCC诊断、预测预后和治疗靶点的生物标志物,在临床上具有广阔的应用前景。本文通过回顾分析cSCC的miRNA表达谱,主要对其中经实验证实表达上调和下调的miRNAs在cSCC中的研究进展作一综述。     

Molecular and immune targets in cutaneous squamous cell carcinoma

Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer and often confers a good prognosis. Though surgery is the gold standard of treatment, unresectable or metastatic disease can necessitate systemic therapy. Of systemic agents, there is increasing interest in the use of immunotherapies and targeted therapy. Further study into the driver mutations in cSCC has identified opportunities for targeted therapy. In this review, we discuss both current and investigational immune and molecular targets of therapy for cSCC.     

Methylthioadenosine phosphorylase expression in cutaneous squamous cell carcinoma

The methylthioadenosine phosphorylase (MTAP) gene is a tumour suppressor gene, located on chromosome 9p21, 100 kb telomeric of the p15 and p16 genes, which are often deleted in tumor cells. The role of MTAP protein expression in the genesis of cutaneous squamous cell carcinoma (SCC) is currently not known. In a previous study we have shown the frequent occurrence of allelic imbalance / loss of heterozygosity (AI/LOH) in cutaneous SCCs using AI/LOH markers flanking the p15, p16, and MTAP genes and demonstrated reduction in p15 and p16 protein expression in comparison to normal human skin. The present study is a continuation to our previous studies, aimed at determining possible roles played by MTAP protein expression in the genesis of cutaneous SCC. The expression of MTAP protein was detected using an immunohistochemical approach in a 109 micro array of cutaneous SCC and 20 normal human skin tissue samples. The expression of MTAP was not significantly different in the cutaneous SCC cases as compared with normal human skin. This may indicate that MTAP protein expression does not contribute to the genesis of cutaneous SCC.     

Adjuvant therapy for advanced renal cell carcinoma

Introduction: Locally advanced, non-metastatic renal cell carcinoma (RCC) is conventionally managed with surgery. However, patients are at a high risk of RCC recurrence and have poor survival outcomes. An effective adjuvant systemic treatment is needed to improve on these outcomes. Targeted molecular and immune-based therapies have been investigated, or are under investigation, but their role in this setting remains unclear.

Areas covered: A comprehensive search of PubMed and ClinicalTrials.gov was performed for relevant literature. The following topics pertinent to adjuvant therapy in RCC were evaluated: strategies for patient selection, cytokine-based immunotherapy, vaccine therapy, VEGF and non-VEGF targeted molecular agents, and immune checkpoint inhibitors.

Expert commentary: Strong evidence for the incorporation of adjuvant therapy in high-risk RCC is lacking. Multiple targeted molecular therapies have been examined with only one approved for use. Genetic and molecular-based prognostic models are needed to determine who may benefit from adjuvant therapy. Developing adjuvant therapy strategies in the future depends on the results of important ongoing trials with immunotherapy and targeted agents.     

Combined modality therapy for oesophageal squamous cell carcinoma

In a prospective study 110 patients with histologically confirmed oesophageal squamous cell carcinoma received radiation therapy combined with bleomycin or a retinoid. Surgery was initially intended in 34 patients and was later on undertaken in 25 of them after irradiation; in 12 patients the operation was regarded as radical and in 4 of these no remaining tumour was found at operation. The survival rate was significantly higher in the operated than in the non-operated patients which entirely depended on the radically operated ones. Survivals up to more than 71 months were observed and the best results were apparently obtained in patients who became tumour-free after preoperative therapy. It is concluded, that the combined treatment was curative only in a few cases and that future studies should be focused on more intensive preoperative treatment and more critical selection of patients for surgery.     

Docetaxel induction therapy in locally advanced squamous cell carcinoma of the head and neck

Patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN) are often treated with induction chemotherapy or chemoradiotherapy, but to date without major impact on survival. The combination of cisplatin-5-fluorouracil (5-FU) (PF) has been used as standard induction therapy; however, poor patient survival has stimulated investigation into new agents with potential activity in SCCHN. Docetaxel has significant single-agent activity in SCCHN and has been investigated in combination with PF regimens as induction therapy. The results of six phase II studies of docetaxel-PF regimens (TPF) as induction in locally advanced SCCHN patients are reviewed and reported. Consistently, high 2-year survival rates and overall response rates were demonstrated across the phase II trials in the range 42-82 and 71-100%, respectively. The toxicity profile seen with TPF-based regimens was acceptable. The primary toxicity was neutropenia, which together with gastrointestinal complaints accounted for the majority of adverse events. Given the encouraging phase II experience with TPF-based regimens, two large-scale phase III studies comparing TPF-based regimens with standard PF regimens are underway. The results have significant potential for validating the findings of the phase II studies, demonstrating improved survival and overall response of patients treated with docetaxel-based induction chemotherapy.     

Combined modality therapy for esophageal squamous cell carcinoma

Of 55 patients with esophageal squamous cell carcinoma, 30 with localized disease were treated with a combined modality for curative intent. Treatment consisted of mitomycin C (10 mg/m2 day 1) and continuous infusion 5-FU (1000 mg/m2 day, days 1-4, 29-32) (CT), radiation (XRT) (3000 rad, days 1-21) with nutritional support, and surgery (days 49-64). Surgery consisted of celiotomy, esophagectomy and esophagogastrostomy +/- postoperative ventilatory support. Postoperative CT plus an additional 2000 rad XRT was restricted to patients with histologic positive tumor. Since five resected patients with subclinical metastatic tumor had an inferior survival equal to 25 patients treated essentially for palliation, pretreatment celiotomy seems warranted to identify patients with an inferior prognosis. Of 18 resected patients without disseminated tumor evaluable for this combined modality: six were tumor free, three had intramural and nine transmural tumor; the median survival is 76 weeks and five of six living patients are disease free at 95-190 weeks; and local recurrence occurred in two and in two of seven unresected patients. Since toxicity was minimal except for postoperative pneumonitis (13%) and local recurrence low (13%), two courses of chemotherapy and 5000 rad XRT perhaps obviates the need for resection.     

晚期肺鳞癌靶向及免疫治疗进展

肺癌是目前世界上发病率和死亡率最高的恶性肿瘤。其中,肺鳞癌（squamous-cell lung cancer,SQCLC）为一种常见的病理类型。近年来,许多学者针对肺鳞癌的靶向药物与免疫制剂进行大量的科学研究及临床试验,EGFR单克隆抗体、VEGFR的单克隆抗体、免疫检查点抑制剂等多种药物已在临床试验中取得了一定成果。本文对晚期肺鳞癌的分子靶向治疗及免疫治疗进行系统性的阐述,通过分析其在提高患者生存率、改善生存质量等方面取得的实质性研究成果,探讨目前临床上晚期肺鳞癌的靶向及免疫治疗进展及未来发展方向。     

Real world safety outcomes using cemiplimab for cutaneous squamous cell carcinoma

IntroductionLocally advanced or metastatic cutaneous squamous cell carcinoma (cSCC) mostly affects older and frail patients. Cemiplimab is an anti-PD1 antibody used in this indication since its approval by the FDA and the EMA in 2019 after encouraging results from phase II trials. We aimed to evaluate cemiplimab safety in patients from daily practice.MethodsRetrospective and monocentric study including all patients who received at least one infusion of cemiplimab between August 2018 and September 2019. Adverse effects (AEs), treatment interruption, and efficacy were recorded (data cut-off, November 1st 2020).ResultsTwenty-two patients were included, median age was 83 [55–93], 73% were Eastern Cooperative Oncology Group (ECOG) 0 or 1, 36% were immune compromised. After a median time on treatment of six months [0.7–22], seventeen patients (77%) experienced 24 AEs, comprising 45% serious AEs (SAEs) grade ≥ 3 and one SAE grade 5 (myositis). Patients who presented SAEs were all >65 years old. Nine patients (41%) definitively discontinued treatment due to AEs. Seventeen patients were evaluable, after a median follow-up of eleven months [1−22], 32% had an objective response (2 complete and 5 partial responses), 47% had controlled disease and 35% experienced progression.ConclusionsIn our cohort, safety seemed to be worse than in phase II trial with more treatment discontinuations due to cemiplimab toxicity, probably reflecting the distinct demographic and medical characteristics of patients in daily care.